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Reports
Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA-levels of Aurora B
Renske J. van Leuken, Mark P. Luna-Vargas, Titia K. Sixma, Rob M.F. Wolthuis and René H. Medema
volume 7 | issue 17
1 September 2008Pages: 2710 - 2719
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Accurate chromosome segregation relies on the mitotic spindle checkpoint. This checkpoint acts to restrict ubiquitin ligase activity of the Anaphase-promoting complex (APC/C) in mitosis until all chromosomes are bipolarly attached to the mitotic spindle. We performed a functional RNAi-based screen to identify De-ubiquitinating enzymes (Dubs) involved in mitotic progression. We identified Usp39 as a new factor required to maintain the spindle checkpoint and support successful cytokinesis. Strikingly, although Usp39 clearly contains an ubiquitin-protease domain, we show that Usp39 is entirely deprived of Dub activity. However, consistent with a previously described role for Usp39 in mRNA processing, we observed specific reduction in Aurora B-mRNA levels after depletion of Usp39. Although we find that exogenously expressed Aurora B cDNA is not sufficient to rescue the checkpoint defect of Usp39-depleted cells, Aurora B expression is restored. Our observations suggest Usp39 to be involved in splicing of Aurora B and other mRNAs that are essential for proper spindle checkpoint function.
Authors
Renske J. van Leuken
University Medical Center Utrecht; Utrecht, The Netherlands
Mark P. Luna-Vargas
The Netherlands Cancer Institute; Amsterdam, The Netherlands
Titia K. Sixma
The Netherlands Cancer Institute; Amsterdam, The Netherlands
Rob M.F. Wolthuis
The Netherlands Cancer Institute; Amsterdam, The Netherlands
René H. Medema
University Medical Center Utrecht; Utrecht, The Netherlands
This is an open-access article
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.